Conformational and electronic factors that influence the balance of agonist and antagonist potencies in different series of opiate narcotics are being investigated by quantum chemical methods. To the end, calculations have been made for a series of oxymorphone derivatives with varying N-substituents; a series of oripavine derivatives with varying C7 alcohol substituents, of 3 phenyl-piperidines with varying C2 plus C3 substituents. The results of extensive conformational calculation indicate the crucial features that could modulate agonist/antagonist potency in each case and help understand differences among them. Calculations of model receptor-N-substituent interactions help to further understand how relative agonist/antagonist potencies can be affected by a combination of N- and C12- substituents. Finally conformations of met-enkephalin have been studied and their similarities to fused ring opiates determined. Work in all these areas is continuing with the goal of prescribing analogues in each series which are mixed agonist/antagonists and hence could be clinically useful, non-addicting analgesics.